Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/108124 https://doi.org/10.1038/cddis.2017.451 |
Resumo: | Transient retinal ischemia is a major complication of retinal degenerative diseases and contributes to visual impairment and blindness. Evidences indicate that microglia-mediated neuroinflammation has a key role in the neurodegenerative process, prompting the hypothesis that the control of microglia reactivity may afford neuroprotection to the retina against the damage induced by ischemia-reperfusion (I-R). The available therapeutic strategies for retinal degenerative diseases have limited potential, but the blockade of adenosine A2A receptor (A2AR) emerges as candidate strategy. Therefore, we evaluated the therapeutic potential of a selective A2AR antagonist (KW6002) against the damage elicited by I-R. The administration of KW6002 after I-R injury reduced microglia reactivity and inflammatory response and afforded protection to the retina. Moreover, we tested the ability of caffeine, an adenosine receptor antagonist, in mediating protection to the retina in the I-R injury model. We demonstrated that caffeine administration dually regulated microglia reactivity and cell death in the transient retinal ischemic model, depending on the reperfusion time. At 24 h of reperfusion, caffeine increased microglial reactivity, inflammatory response and cell death elicited by I-R. However, at 7 days of reperfusion, caffeine administration decreased microglia reactivity and reduced the levels of proinflammatory cytokines and cell death. Together, these results provide a novel evidence for the use of adenosine A2AR antagonists as potential therapy for retinal ischemic diseases and demonstrate the effect of caffeine on the regulation of microglia-mediated neuroinflammation in the transient ischemic model. |
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Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damageAdenosineAdenosine A2 Receptor AntagonistsAnimalsCaffeineHumansInflammationIschemiaMaleMicrogliaNitrobenzenesPyridinesRatsReceptor, Adenosine A2AReperfusion InjuryRetinaRetinal DiseasesTransient retinal ischemia is a major complication of retinal degenerative diseases and contributes to visual impairment and blindness. Evidences indicate that microglia-mediated neuroinflammation has a key role in the neurodegenerative process, prompting the hypothesis that the control of microglia reactivity may afford neuroprotection to the retina against the damage induced by ischemia-reperfusion (I-R). The available therapeutic strategies for retinal degenerative diseases have limited potential, but the blockade of adenosine A2A receptor (A2AR) emerges as candidate strategy. Therefore, we evaluated the therapeutic potential of a selective A2AR antagonist (KW6002) against the damage elicited by I-R. The administration of KW6002 after I-R injury reduced microglia reactivity and inflammatory response and afforded protection to the retina. Moreover, we tested the ability of caffeine, an adenosine receptor antagonist, in mediating protection to the retina in the I-R injury model. We demonstrated that caffeine administration dually regulated microglia reactivity and cell death in the transient retinal ischemic model, depending on the reperfusion time. At 24 h of reperfusion, caffeine increased microglial reactivity, inflammatory response and cell death elicited by I-R. However, at 7 days of reperfusion, caffeine administration decreased microglia reactivity and reduced the levels of proinflammatory cytokines and cell death. Together, these results provide a novel evidence for the use of adenosine A2AR antagonists as potential therapy for retinal ischemic diseases and demonstrate the effect of caffeine on the regulation of microglia-mediated neuroinflammation in the transient ischemic model.Springer Nature2017-10-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108124http://hdl.handle.net/10316/108124https://doi.org/10.1038/cddis.2017.451eng2041-4889Boia, RaquelElvas, FilipeMadeira, Maria H.Aires, Inês D.Rodrigues-Neves, Ana C.Tralhão, PedroSzabó, Eszter CBaqi, YounisMüller, Christa E.Tomé, Ângelo R.Cunha, Rodrigo A.Ambrósio, FranciscoSantiago, Ana R.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-11T17:16:30Zoai:estudogeral.uc.pt:10316/108124Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:23.458468Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage |
title |
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage |
spellingShingle |
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage Boia, Raquel Adenosine Adenosine A2 Receptor Antagonists Animals Caffeine Humans Inflammation Ischemia Male Microglia Nitrobenzenes Pyridines Rats Receptor, Adenosine A2A Reperfusion Injury Retina Retinal Diseases |
title_short |
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage |
title_full |
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage |
title_fullStr |
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage |
title_full_unstemmed |
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage |
title_sort |
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage |
author |
Boia, Raquel |
author_facet |
Boia, Raquel Elvas, Filipe Madeira, Maria H. Aires, Inês D. Rodrigues-Neves, Ana C. Tralhão, Pedro Szabó, Eszter C Baqi, Younis Müller, Christa E. Tomé, Ângelo R. Cunha, Rodrigo A. Ambrósio, Francisco Santiago, Ana R. |
author_role |
author |
author2 |
Elvas, Filipe Madeira, Maria H. Aires, Inês D. Rodrigues-Neves, Ana C. Tralhão, Pedro Szabó, Eszter C Baqi, Younis Müller, Christa E. Tomé, Ângelo R. Cunha, Rodrigo A. Ambrósio, Francisco Santiago, Ana R. |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Boia, Raquel Elvas, Filipe Madeira, Maria H. Aires, Inês D. Rodrigues-Neves, Ana C. Tralhão, Pedro Szabó, Eszter C Baqi, Younis Müller, Christa E. Tomé, Ângelo R. Cunha, Rodrigo A. Ambrósio, Francisco Santiago, Ana R. |
dc.subject.por.fl_str_mv |
Adenosine Adenosine A2 Receptor Antagonists Animals Caffeine Humans Inflammation Ischemia Male Microglia Nitrobenzenes Pyridines Rats Receptor, Adenosine A2A Reperfusion Injury Retina Retinal Diseases |
topic |
Adenosine Adenosine A2 Receptor Antagonists Animals Caffeine Humans Inflammation Ischemia Male Microglia Nitrobenzenes Pyridines Rats Receptor, Adenosine A2A Reperfusion Injury Retina Retinal Diseases |
description |
Transient retinal ischemia is a major complication of retinal degenerative diseases and contributes to visual impairment and blindness. Evidences indicate that microglia-mediated neuroinflammation has a key role in the neurodegenerative process, prompting the hypothesis that the control of microglia reactivity may afford neuroprotection to the retina against the damage induced by ischemia-reperfusion (I-R). The available therapeutic strategies for retinal degenerative diseases have limited potential, but the blockade of adenosine A2A receptor (A2AR) emerges as candidate strategy. Therefore, we evaluated the therapeutic potential of a selective A2AR antagonist (KW6002) against the damage elicited by I-R. The administration of KW6002 after I-R injury reduced microglia reactivity and inflammatory response and afforded protection to the retina. Moreover, we tested the ability of caffeine, an adenosine receptor antagonist, in mediating protection to the retina in the I-R injury model. We demonstrated that caffeine administration dually regulated microglia reactivity and cell death in the transient retinal ischemic model, depending on the reperfusion time. At 24 h of reperfusion, caffeine increased microglial reactivity, inflammatory response and cell death elicited by I-R. However, at 7 days of reperfusion, caffeine administration decreased microglia reactivity and reduced the levels of proinflammatory cytokines and cell death. Together, these results provide a novel evidence for the use of adenosine A2AR antagonists as potential therapy for retinal ischemic diseases and demonstrate the effect of caffeine on the regulation of microglia-mediated neuroinflammation in the transient ischemic model. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-10-05 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/108124 http://hdl.handle.net/10316/108124 https://doi.org/10.1038/cddis.2017.451 |
url |
http://hdl.handle.net/10316/108124 https://doi.org/10.1038/cddis.2017.451 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2041-4889 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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